
Evaluations in the TRAMP Prostate Cancer Model
Oncotarget
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Harnessing Bacteria for Immune Response in Prostate Cancer
The chapter explores using immunogenic bacteria to recruit immune cells and activate cancer-fighting immune responses within the tumor microenvironment of prostate cancer. Positive results show reduced disease burden when coupling the bacteria with antibodies that block immune signaling, with potential applications in other cancer types like pancreatic cancer.
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Oncotarget recently published "Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model" which reported that the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer.
CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals.
In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable.
Combination of CRC2631 with checkpoint blockade reduces metastasis burden.
Collectively, these Oncotarget findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.
Dr. Yves C. Chabu from The University of Missouri said, "Conventional cancer chemotherapies are not specific and, as such, generate significant morbidities."
Several bacterial strains have been developed, including the Salmonella enterica serovar Typhimurium strain VNP20009, one of the most studied tumor-targeting strains.
VNP20009 was first isolated in a genetic screen for hyper invasion mutants using a library of mutant strains derived from ultraviolet and chemical mutagenesis of strain 14028.
CRC2631 was derived from a parent strain that was derived from the prototrophic wild-type Salmonella typhimurium LT2 strain.
This collection consists of mutant strains that arose naturally under nutrient-limiting conditions for over four decades, generating a wealth of genetically diverse and potentially attenuated strains.
Similar to prostate cancers in men, these murine carcinomas disseminate throughout visceral organs, differentiate into neuroendocrine prostate cancer, and ultimately kill the host.
The Chabu Research Team concluded in their Oncotarget Research Paper, "Importantly, CRC2631 reduced metastasis incidence in the setting of checkpoint blockade. This is significant because metastasis is the main cause of cancer-associated deaths and no effective immunotherapy against prostate cancer currently exist."
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DOI - https://doi.org/10.18632/oncotarget.27769
Full text - https://www.oncotarget.com/article/27769/text/
Correspondence to - Yves C. Chabu - chabuc@missouri.edu
Keywords - salmonella, cancer targeting, prostate cancer, immunotherapy, TRAMP
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